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Anatomical Sciences > Cytoskeleton > Flashcards

Cytoskeleton Flashcards

1
Q

What is the real version of the cell?

A

The cell is a complex system controlled on a sub-second time scale over sub- to thousands of microns

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2
Q

The cytoskeleton is…

A

The skeleton and muscles of cells

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3
Q

Define the cytoskeleton

A

A system of protein polymers that allow:

  1. architecture
  2. shape
  3. motility of cells
  4. directed movement of organelles and molecules in the cell
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4
Q

Components of the cytoskeleton

A

Microtubules
Microfilaments (actin filaments)
Intermediate filaments
Host of accessory and regulatory proteins

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5
Q

Polymers of tubulin dimers made up _____ and _____

A

Polymers of tubulin dimers made up alpha-tubulin and beta-tubulin

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6
Q

Tubulin is what kind of enzyme

A

A GTPase

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7
Q

Is tubulin solid or hollow and describe more

A

Hollow with outer diameter of 24 nm

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8
Q

What proteins stabilize and space the polymers and regulate interactions between cytoskeletal elements?

A

Accessory proteins called microtubule-associated proteins (MAPs)

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9
Q

What are properties of microtubules?

A

Highly dynamic if not stabilized (can undergo rapid bouts of assembly and disassembly)

Act as substrate for microtubule-based proteins to transport cargo (organelles)

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10
Q

Describe the structure of microtubules

A

Polarized polymer with a plus and minus end

Plus end = dynamic (lengthens and shortens)

Motor proteins read the polarity and go to one end or the other

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11
Q

Functions of microtubules are…

A
  1. Make up the mitotic spindle
  2. Provide railways for organelle transport in most interphase cells
  3. Key determinant of cell shape
  4. Important in neurons for cell shape and axonal transport
  5. Provide the backbone for cilia and flagella
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12
Q

How many protofilaments are microtubules made of?

A

13 (+_)

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13
Q

What are protofilaments?

A

Stacks of tubulin dimers

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14
Q

What end is dynein directed towards?

A

Minus end

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15
Q

What end is kinesin directed towards?

A

+ end

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16
Q

Microtubule Associated Proteins are

A

Structural non-motor proteins

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17
Q

What are the functions of MAPs?

A

Organize MTs

Regulate MTs stability

Regulate MT dynamics

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18
Q

What is nucleation?

A

Genesis of a cytoskeletal polymer

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19
Q

Polymerization

A

The elongation of a cytoskeletal polymer following the initial nucleation

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20
Q

Nucleation for MTs occurs where?

A

Centrosome

Recent research indicates that golgi fragments may also nucleate MTs

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21
Q

Gamma tubulin in centrosome is only required for what?

A

Nucleation

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22
Q

The basal body is what?

A

A microtubule organizing center for cilia and flagella

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23
Q

What is a 9+2 structure of cilia and flagella?

A

The axoneme

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24
Q

What drives axonemal motility?

A

Dynein

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25
Q

Immotile Cilia Syndrome

A

A body-wide defect in axonemal structure that result in obstructive lung disease and sterile males

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26
Q

Kartagener’s Syndrome

A

A combination of Situs inversus (reversal of normal body asymmetry) and Immotile Cilia Syndrome

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27
Q

Cancer

A

Target for therapeutics, e.g. disruption of MT dynamics to block cell division (e.g., Taxol)

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28
Q

Diseases associated with malfunction of microtubule based cellular structures

A

Immotile Cilia Syndrome

Kartagener’s syndrome

Cancer

Lissencephaly

Charcot-Marie-Tooth disease type 2A

Neurodegenerative disorders

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29
Q

Lissencephaly

A

Mutations in microtubule proteins LIS1 and doublecortin

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30
Q

Charcot-Marie-Tooth disease type 2A

A

Mutation in specific kinesin has been reported in one case

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31
Q

What occurs in neurodegenerative disorders related to cytoskeleton?

A

Abnormalities/mutations in tau, dynein, kinesin, spastin

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32
Q

What do neurotopic viruses do?

A

Exploit neuron’s microtubule based transport system to reach cell bodies

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33
Q

Microfilaments are

A

Non-hollow polymers of the globular protein actin

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34
Q

Actin is what type of enzyme?

A

ATPase

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35
Q

What shape is actin?

A

Helical

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36
Q

Diameter of actin

A

Roughly 7 nm

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37
Q

Properties of actin

A
  1. Highly dynamic if not stabilized; undergo rapid bouts of assembly and disassembly
  2. Variety of configurations regulated by accessory proteins
  3. Substrate for members of the myosin family of motors to transport cargo
  4. Unlike microtubules, actin filaments don’t have specific organizing centers like centrosome and can be nucleated almost anywhere in the cell
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38
Q

Structure of microfilaments (describe both ends)

A

Polarized filament with barbed end and pointed end

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39
Q

For actin which end is favoured for assembly?

A

Barbed end

40
Q

Myosin and polarity of microfilaments

A

Myosin motors read the polarity and move toward one end or the other (most move toward + end)

41
Q

Functions of microfilaments

A
  1. Concentrated in cell cortex for various functions
  2. Cleavage furrow for pinching off cells in final stages of mitosis
  3. Cell motility
  4. Short-range organelle transport
  5. Contractility (in both muscle and non-muscle)
42
Q

What are 3 actin isoforms?

A

Alpha, beta, and gamma

43
Q

Alpha actin is _____ _____

A

Muscle specific

44
Q

Beta and gamma are found in ___ ____

A

Most cells

45
Q

For nucleation and polymerization, actin must be…

A

ATP loaded

46
Q

Myosins

A

F-actin associated force generating mechanoenzymes with roles in contractility and intracellular transport

47
Q

Most myosins move toward which end of filaments?

A

barbed end

48
Q

Microvilli

A

Actin based epithelial projections

49
Q

F-actin and myosin II are located at the ___ ___ during cell division

A

contractile ring

50
Q

F-actin serves as ____ for spectrin web

A

scaffold

51
Q

Diseases association with malfunction of actin based cellular structures

A
  1. Hereditary spherocytosis
  2. Hereditary elliptocytosis
  3. Breast cancer
  4. Familial hypertropic cardiomyopathy
  5. Mutations in skeletal muscle actin
52
Q

Hereditary spherocytosis

A

Deforms RBCs to fragile spherocytes bc of weakened binding affinity of spectrin to band 4.1

53
Q

Hereditary elliptocytosis

A

Deforms red cells to fragile elliptocytes bc of incomplete formation of spectrin

54
Q

Breast cancer

A

In some forms, actin associated protein Tensin, which links integrin receptors to actin cytoskeleton, is disrupted promoting metastatic migration of cancerous cells

55
Q

Mutations in skeletal muscle actin

A

Associated with congenital myopathies characterized by structural abnormalities of the muscle and variable degrees of muscle weakness

56
Q

Myosin VI mutations

A

Cause deafness

57
Q

Myosin VII mutations

A

Associated with deafness, neurological disorder, and blindness

58
Q

Pathogens take the endogenous actin machinery to…

A

Translocate within cells

59
Q

Phalloidin from amanita phalloides (fungi)

A

Binds to and stabilizes actin filaments

60
Q

Intermediate filaments structure

A

Non-polarized

Roughly 10 nm in diameter

Comparatively non-dynamic - much more stable

61
Q

Functions of intermediate filaments

A
  1. Space-filling elements
  2. Give tensile strength
  3. Specialized functions depending on cell type
  4. Important at cell junctions
62
Q

Intermediate filaments are much _____ _____ across cell types than microtubules or microfilaments

A

less conserved

63
Q

Can different cells have different intermediate filaments? What can they be used for?

A

Yes and can be used as cell-specific “markers”

64
Q

Diseases associated with malfunction of intermediate filament based cellular structures

A
  1. Epidermolysis bullosa simplex
  2. Progeria
65
Q

Epidermolysis bullosa simplex

A

Mutation in keratin genes expressed in basal cell layer of epidermis, result in a skin that is very sensitive to mechanical injury

66
Q

Progeria

A

‘Fast aging disease’ associated with a mutation in nuclear lamin protein

67
Q

How many distinct diseases have been associated with the intermediate filament gene family?

A

76

68
Q

Keratins are mutated in more than __ diseases

A

20

69
Q

Desmin is mutated in _________

A

cardiomyopathies

70
Q

Neurofilament proteins

A

Small subunit mutated in the IF/2E forms of Charcot-Marie Tooth Disease

71
Q

Periphin

A

Induced after peripheral nerve injury

72
Q

Glial Fibrillary Acidic Protein

A

Mutated in Alexander disease (leukodystrophy resulting in abnormal myelin)

73
Q

Arp2/3 binds to…

A

Pre-existing filament

74
Q

Describe parts of microvilli

A
  1. Barbed end always found at tip
  2. Actin filaments
  3. Lateral arm (myosin I-calmodulin): myosin I used
    as structural protein
  4. Villin fimbrin: make sure filaments are nicely
    arranged
  5. Terminal web at bottom
75
Q

Describe structures of Myosin I, II, and V

A

Myosin I: has calmodulin light chains (monomeric so only 1 heavy chain)

Myosin II: has regulatory light chain and essential light chain (dimeric)

Myosin V: has calmodulin light chains (dimeric)

76
Q

Formins and Spire make what?

A

Individuals filaments - do not need prior filaments

77
Q

Give 2 examples of pathogen using endogenous actin machinery to translocate within cells

A

Listeria monocytogenes infection

Shigella flexneri infection

78
Q

List 3 leading edge meshworks

A

Arp 2/3
Profilin
Cofilin

79
Q

List 3 stress fibers

A

Myosin
Alpha-actinin
Formins

80
Q

Periphery actin filaments are nucleated by…

A

Arp2/3

81
Q

Center of cell nucleated by…

A

Formins

82
Q

The ability of cell to migrate is dependent on what?

A

Actin cytoskeleton

83
Q

There is a physical link between the actin cytoskeleton and…

A

The extracellular environment

84
Q

Describe kinesin structure

A

Light chains, heavy chains, coiled coil, and head domain

85
Q

Describe dynein structure

A

Light, heavy, intermediate chains, and head domain

86
Q

Give an example of a neurotopic virus

A

Herpes virus

87
Q

What do light and intermediate chains of dynein do?

A

Regulate function & control what it’s bound to

88
Q

What are 2 MAPs?

A

Kinesin and dynein

89
Q

Where is mucociliary escalator found?

A

Along airways

90
Q

Dynein allows for what in MTs?

A

Allows MTs to bend by sliding them relative to one another

91
Q

What does cancer drug Taxol do to MTs?

A

Binds MTs and stabilizes so they no longer have dynamic instability

92
Q

Rabies virus binds dynein or kinesin?

A

Dynein when going to minus end where cell body is then goes on kinesin to go to nerve ending to release particles and cycle repeats

93
Q

Why do myosin VI mutations cause deafness?

A

Prevent formation of the proper structure of stereocilia in inner ear

94
Q

What is basic subunit of intermediate filament?

A

Tetramer

95
Q
A

Anatomical Sciences (4 decks)

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